Synthesis and anxiolytic activity of 1-phenyl-2-(4-aryl-1,3,4,5-tetrahydropyrido[2,3-b][1 ,4]diazepin-2-ylidene)-ethanone

A two-step, general synthesis of 1-phenyl-2-(4-aryl-1,3,4,5-tetrahydropyrido2,3-b]1,4]diazepin-2-ylidene)-ethanones 3-9 is presented. This synthesis employs a condensation of 2,3-diaminopyridine with benzoylacetone followed by a basic-activated cyclization reaction with substituted benzaldehydes for final closure of the seven-membered ring. Molecular diversity is fixed by appropriate aldehydes: 2-chloro-, 4-chloro-, 2-bromo-, 4-bromo-, 4-fluoro-, 4-trifluoro- and 3-bromo-4,5-dimethoxybenzaldehyde. Compounds 4, 6, 8, 9 and 10 were examined for their anxiolytic activity. The most active was the compound with the chlorophenyl substituent i.e. 1-phenyl-2-{4-(4-chlorophenyl)-1,3,4,5-tetrahydropyrido2,3-b]1,4]diazepin-2-ylidene}-ethanone (4).